Premium
Hyperpolarized [ 13 C]ketobutyrate, a molecular analog of pyruvate with modified specificity for LDH isoforms
Author(s) -
von Morze Cornelius,
Bok Robert A.,
Ohliger Michael A.,
Zhu Zihan,
Vigneron Daniel B.,
Kurhanewicz John
Publication year - 2016
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.25716
Subject(s) - in vivo , lactate dehydrogenase , chemistry , enzyme , biochemistry , gene isoform , in vitro , isozyme , pyruvate dehydrogenase complex , microbiology and biotechnology , biology , gene
Purpose The purpose of this study was to investigate 13 C hyperpolarization of α‐ketobutyrate (αKB), an endogenous molecular analog of pyruvate, and its in vivo enzymatic conversion via lactate dehydrogenase (LDH) using localized MR spectroscopy. Methods Hyperpolarized (HP) 13 C MR experiments were conducted using [ 13 C]αKB with rats in vivo and with isolated LDH enzyme in vitro, along with comparative experiments using [ 13 C]pyruvate. Based on differences in the kinetics of its reaction with individual LDH isoforms, HP [ 13 C]αKB was investigated as a novel MR probe, with added specificity for activity of LDHB‐expressed H (“heart”‐type) subunits of LDH (e.g., constituents of LDH‐1 isoform). Results Comparable T 1 and polarization values to pyruvate were attained (T 1 = 52 s at 3 tesla [T], polarization = 10%, at C 1 ). MR experiments showed rapid enzymatic conversion with substantially increased specificity. Formation of product HP [ 13 C]α‐hydroxybutyrate (αHB) from αKB in vivo was increased 2.7‐fold in cardiac slabs relative to liver and kidney slabs. In vitro studies resulted in 5.0‐fold higher product production from αKB with bovine heart LDH‐1, as compared with pyruvate. Conclusions HP [ 13 C]αKB may be a useful MR probe of cardiac metabolism and other applications where the role of H subunits of LDH is significant (e.g., renal cortex and brain). Magn Reson Med 75:1894–1900, 2016. © 2015 Wiley Periodicals, Inc.